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This clinical research studies the physiology and immunology of new-onset post-transplant diabetes mellitus in patients undergoing allogeneic stem cell transplantation. Oral glucose tolerance tests (OGTT), hyperglycemic clamps, and immune assays will be used to define the mechanisms associated with abnormal glucose homeostasis following stem cell transplantation. Information from this clinical trial could be used to develop standardized screening procedures or to develop optimal treatment strategies for patients developing post-transplant diabetes mellitus.
PRIMARY OBJECTIVES:
I. To determine if changes in islet cell physiology are detectable before or after matched related donor (MRD) hematopoietic stem cell transplant (HCT) in patients developing new-onset post-transplant diabetes mellitus (PTDM).
II. To determine if the IL-33/ST2 axis promotes immune/islet cell dysregulation during PTDM.
OUTLINE:
Patients undergo 2 OGTTs and a standard hyperglycemic clamp procedure prior to HCT. Patients then undergo repeat OGTTs and a hyperglycemic clamp procedure once after HCT between days 80-100.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 for MRD HCT Recipients | Patients undergo an Oral Glucose Tolerance Test (OGTT) and 1 hyperglycemic clamp will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant. |
| |
| Arm 2 for MRD HCT Recipients | Patients undergo 2 Oral Glucose Tolerance Test (OGTTs) (with and without GLP-1 analogue) will be performed on separate days prior to transplant and then each procedure will be repeated once between day+80 to day+100 (+/- 10 days) after transplant. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Drug | A standard OGTT will be performed. During OGTT 75gm of glucose will be given followed by phlebotomy. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (univariable analysis). | A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in GSIS between these two groups. | Up to 28 days pre-transplant |
| Pre-transplant insulin secretion will be measured as glucose stimulated insulin secretion (GSIS) during a hyperglycemic clamp procedure among patients who do or do not go on to develop PTDM (multivariable analysis). | A hyperglycemic clamp procedure will be performed pre-transplant. Pre-transplant will be defined as no more than 28 days before allogeneic hematopoietic cell transplantation. Patients will then be followed for 100 days after transplant for development of diabetes. In multivariable analysis, logistic regression will evaluate whether GSIS is an independent predictor of PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association. | Up to 28 days pre-transplant |
| Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (univariable analysis). | Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in glucagon secretion between these two groups. | Up to 100 days after transplant |
| Post-transplant glucagon secretion will be measured during the oral glucose tolerance test among patients who do or do not develop PTDM (multivariable analysis). |
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Inclusion Criteria for Patients:
Exclusion Criteria for Patients:
Additional exclusion criteria (Arms 1 and 2 Aim 1 only):
-Diagnosis of diabetes by standard oral glucose tolerance testing prior to transplant (2-hour plasma glucose value ≥ 200 mg/dL) in either Arm 1 or 2 will exclude further testing as per Aim 1. Immunological / metabolic testing as per Aim 2 will still be allowed
DONORS Inclusion Criteria for Donors (Arm 1 and Arm 2) Donors undergoing stem cell collection for related allogeneic stem cell transplant
Exclusion Criteria for Donors (Arms 1 and 2):
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Patients without a history of diabetes mellitus undergoing allogeneic hematopoietic stem cell transplantation (HCT).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| VICC Clinical Trials Information Program | Contact | 800-811-8480 | brian.engelhardt@vumc.org | |
| Brian G. Engelhardt, M.D. | Contact | 615 936-0381 | brian.engelhardt@vumc.org |
| Name | Affiliation | Role |
|---|---|---|
| Brian G. Engelhardt, M.D. | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37232 | United States |
| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 4, 2025 | |
| Reset | Sep 24, 2025 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 1, 2017 |
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Serum / plasma and peripheral blood mononuclear cells will be collected before and after hematopoietic stem cell transplant (HCT)
| 2 OGTTs with and without GLP-1 analogue | Drug | A standard OGTT will be performed and a second OGTT procedure will be repeated on a different day with GLP-1 analogue. |
|
| Hyperglycemic clamp procedure | Drug | During the hyperglycemic clamp procedure, D20 will given, followed by phlebotomy. |
|
Patients will be followed for 100 days after transplant for development of diabetes. In multivariable analysis, a logistic regression will evaluate whether glucagon secretion is independently associated with PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association. |
| Up to 100 days after transplant |
| Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (univariable analysis). | Patients will be followed for 100 days after transplant for development of diabetes. In univariable analysis, a Wilcoxon rank sum test will be applied to compare the population mean difference in IL-33 between these two groups. | Up to 100 days after transplant |
| Plasma IL-33 levels will be measured among patients who do or do not develop PTDM (multivariable analysis). | In multivariable analysis, logistic regression will evaluate whether IL-33 is independently associated with PTDM after adjusting for the following covariates: gender, conditioning (ablative vs. reduced intensity), or acute graft-versus-host disease (GVHD) requiring steroids. The estimated odds ratio (OR) and 95% confidence interval of the OR will be provided to measure the effect of the association. | Up to 100 days after transplant |
| Jan 15, 2018 |
| Prot_SAP_000.pdf |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 4, 2025 | Sep 24, 2025 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |
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